{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T16:16:33Z","timestamp":1764519393722},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Projekt DEAL"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The determinants of brown adipose tissue (BAT) activity are not yet known in detail but might serve as future therapeutic targets against obesity and the metabolic syndrome. We analyzed 235\u00a0datasets of lymphoma patients with two PET\/CT examinations at different time points retrospectively. We assessed the anthropometric characteristics, features related to the metabolic syndrome, thyroid dysfunction, season of the PET\/CT examination, weight change, prior cancer history, lymphoma subgroups, disease activity, and specific lymphoma-related therapies, and evaluated their association with BAT activity. We found BAT activity in 12% of all examinations, and the incidence of BAT activity after initially negative examinations was 10%. In multivariate regression analysis, the prevalence of BAT activity was associated with age, body mass index, sex, the season of the examination, diabetes mellitus, arterial hypertension, and medication on the beta-receptors. New BAT activity arose more often in patients without preceding lymphoma-related therapy. No specific medication was associated with BAT activity. In conclusion, this study confirms the potential connection of BAT with the metabolic syndrome. Preceding lymphoma-related therapy might have an inhibitory effect on the recruitment of BAT.<\/jats:p>","DOI":"10.1038\/s41598-020-78419-7","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T11:20:56Z","timestamp":1607685656000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Determinants of activity of brown adipose tissue in lymphoma patients"],"prefix":"10.1038","volume":"10","author":[{"given":"Cornelia","family":"Brendle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Stefan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Grams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Soekler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"la Foug\u00e8re","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Pfannenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"78419_CR1","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/nature13477","volume":"510","author":"V Peirce","year":"2014","unstructured":"Peirce, V., Carobbio, S. & Vidal-Puig, A. The different shades of fat. Nature 510, 76\u201383. https:\/\/doi.org\/10.1038\/nature13477 (2014).","journal-title":"Nature"},{"key":"78419_CR2","doi-asserted-by":"publisher","first-page":"447","DOI":"10.3389\/fendo.2018.00447","volume":"9","author":"AC Carpentier","year":"2018","unstructured":"Carpentier, A. C. et al. Brown adipose tissue energy metabolism in humans. Front. Endocrinol. 9, 447. https:\/\/doi.org\/10.3389\/fendo.2018.00447 (2018).","journal-title":"Front. Endocrinol."},{"key":"78419_CR3","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/nm.3017","volume":"19","author":"ME Lidell","year":"2013","unstructured":"Lidell, M. E. et al. Evidence for two types of brown adipose tissue in humans. Nat. Med. 19, 631\u2013634. https:\/\/doi.org\/10.1038\/nm.3017 (2013).","journal-title":"Nat. Med."},{"key":"78419_CR4","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1007\/s00259-002-0902-6","volume":"29","author":"TF Hany","year":"2002","unstructured":"Hany, T. F. et al. Brown adipose tissue: A factor to consider in symmetrical tracer uptake in the neck and upper chest region. Eur. J. Nucl. Med. Mol. Imaging. 29, 1393\u20131398. https:\/\/doi.org\/10.1007\/s00259-002-0902-6 (2002).","journal-title":"Eur. J. Nucl. Med. Mol. Imaging."},{"key":"78419_CR5","first-page":"1267","volume":"44","author":"C Cohade","year":"2003","unstructured":"Cohade, C., Mourtzikos, K. A. & Wahl, R. L. \u201cUSA-Fat\u201d: Prevalence is related to ambient outdoor temperature-evaluation with 18F-FDG PET\/CT. J. Nucl. Med. 44, 1267\u20131270 (2003).","journal-title":"J. Nucl. Med."},{"key":"78419_CR6","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1056\/NEJMoa0810780","volume":"360","author":"AM Cypess","year":"2009","unstructured":"Cypess, A. M. et al. Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360, 1509\u20131517. https:\/\/doi.org\/10.1056\/NEJMoa0810780 (2009).","journal-title":"N. Engl. J. Med."},{"key":"78419_CR7","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.cmet.2016.07.014","volume":"24","author":"KY Chen","year":"2016","unstructured":"Chen, K. Y. et al. Brown adipose reporting criteria in imaging STudies (BARCIST 1.0): Recommendations for standardized FDG-PET\/CT experiments in humans. Cell Metab. 24, 210\u2013222. https:\/\/doi.org\/10.1016\/j.cmet.2016.07.014 (2016).","journal-title":"Cell Metab."},{"key":"78419_CR8","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1111\/brv.12389","volume":"93","author":"P Tapia","year":"2018","unstructured":"Tapia, P. et al. Biology and pathological implications of brown adipose tissue: Promises and caveats for the control of obesity and its associated complications. Biol. Rev. Camb. Philos. Soc. 93, 1145\u20131164. https:\/\/doi.org\/10.1111\/brv.12389 (2018).","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"78419_CR9","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s13679-017-0283-6","volume":"6","author":"KL Marlatt","year":"2017","unstructured":"Marlatt, K. L. & Ravussin, E. Brown adipose tissue: An update on recent findings. Curr. Obes. Rep. 6, 389\u2013396. https:\/\/doi.org\/10.1007\/s13679-017-0283-6 (2017).","journal-title":"Curr. Obes. Rep."},{"key":"78419_CR10","doi-asserted-by":"publisher","first-page":"20170093","DOI":"10.1259\/bjr.20170093","volume":"90","author":"JD Steinberg","year":"2017","unstructured":"Steinberg, J. D., Vogel, W. & Vegt, E. Factors influencing brown fat activation in FDG PET\/CT: A retrospective analysis of 15,000+ cases. Br. J. Radiol. 90, 20170093. https:\/\/doi.org\/10.1259\/bjr.20170093 (2017).","journal-title":"Br. J. Radiol."},{"key":"78419_CR11","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.2337\/db10-0004","volume":"59","author":"C Pfannenberg","year":"2010","unstructured":"Pfannenberg, C. et al. Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans. Diabetes 59, 1789\u20131793. https:\/\/doi.org\/10.2337\/db10-0004 (2010).","journal-title":"Diabetes"},{"key":"78419_CR12","doi-asserted-by":"publisher","first-page":"793039","DOI":"10.1100\/2012\/793039","volume":"2012","author":"YC Huang","year":"2012","unstructured":"Huang, Y. C. et al. Review analysis of the association between the prevalence of activated brown adipose tissue and outdoor temperature. Sci. World J. 2012, 793039. https:\/\/doi.org\/10.1100\/2012\/793039 (2012).","journal-title":"Sci. World J."},{"key":"78419_CR13","doi-asserted-by":"publisher","first-page":"e101653","DOI":"10.1371\/journal.pone.0101653","volume":"9","author":"MJ Vosselman","year":"2014","unstructured":"Vosselman, M. J., Vijgen, G. H., Kingma, B. R., Brans, B. & van Marken Lichtenbelt, W. D. Frequent extreme cold exposure and brown fat and cold-induced thermogenesis: A study in a monozygotic twin. PLoS\u00a0One 9, e101653. https:\/\/doi.org\/10.1371\/journal.pone.0101653 (2014).","journal-title":"PLoS\u00a0One"},{"key":"78419_CR14","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s40246-019-0239-x","volume":"13","author":"Y Pan","year":"2019","unstructured":"Pan, Y., Liu, J. & Qi, F. Identification of key candidate genes and molecular pathways in white fat browning: An anti-obesity drug discovery based on computational biology. Hum. Genom. 13, 55. https:\/\/doi.org\/10.1186\/s40246-019-0239-x (2019).","journal-title":"Hum. Genom."},{"key":"78419_CR15","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.ebiom.2018.10.019","volume":"37","author":"Y Qiu","year":"2018","unstructured":"Qiu, Y. et al. Screening of FDA-approved drugs identifies sutent as a modulator of UCP1 expression in brown adipose tissue. EBioMedicine 37, 344\u2013355. https:\/\/doi.org\/10.1016\/j.ebiom.2018.10.019 (2018).","journal-title":"EBioMedicine"},{"key":"78419_CR16","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1111\/obr.12584","volume":"18","author":"RKC Loh","year":"2017","unstructured":"Loh, R. K. C., Kingwell, B. A. & Carey, A. L. Human brown adipose tissue as a target for obesity management; beyond cold-induced thermogenesis. Obes. Rev. 18, 1227\u20131242. https:\/\/doi.org\/10.1111\/obr.12584 (2017).","journal-title":"Obes. Rev."},{"key":"78419_CR17","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.cmet.2014.12.009","volume":"21","author":"AM Cypess","year":"2015","unstructured":"Cypess, A. M. et al. Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab. 21, 33\u201338. https:\/\/doi.org\/10.1016\/j.cmet.2014.12.009 (2015).","journal-title":"Cell Metab."},{"key":"78419_CR18","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.121510","author":"BS Finlin","year":"2018","unstructured":"Finlin, B. S. et al. Human adipose beiging in response to cold and mirabegron. JCI Insight. https:\/\/doi.org\/10.1172\/jci.insight.121510 (2018).","journal-title":"JCI Insight."},{"key":"78419_CR19","doi-asserted-by":"publisher","first-page":"947","DOI":"10.2337\/db18-0956","volume":"68","author":"B Halpern","year":"2019","unstructured":"Halpern, B. et al. Melatonin increases brown adipose tissue volume and activity in patients with melatonin deficiency: A proof-of-concept study. Diabetes 68, 947\u2013952. https:\/\/doi.org\/10.2337\/db18-0956 (2019).","journal-title":"Diabetes"},{"key":"78419_CR20","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1097\/MOL.0b013e32835a4f40","volume":"24","author":"M Saito","year":"2013","unstructured":"Saito, M. & Yoneshiro, T. Capsinoids and related food ingredients activating brown fat thermogenesis and reducing body fat in humans. Curr. Opin. Lipidol. 24, 71\u201377. https:\/\/doi.org\/10.1097\/MOL.0b013e32835a4f40 (2013).","journal-title":"Curr. Opin. Lipidol."},{"key":"78419_CR21","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1111\/dom.13157","volume":"20","author":"M Thuzar","year":"2018","unstructured":"Thuzar, M. et al. Glucocorticoids suppress brown adipose tissue function in humans: A double-blind placebo-controlled study. Diabetes Obes. Metab. 20, 840\u2013848. https:\/\/doi.org\/10.1111\/dom.13157 (2018).","journal-title":"Diabetes Obes. Metab."},{"key":"78419_CR22","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.metabol.2017.01.024","volume":"70","author":"H Scotney","year":"2017","unstructured":"Scotney, H. et al. Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo. Metab. Clin. Exp. 70, 125\u2013132. https:\/\/doi.org\/10.1016\/j.metabol.2017.01.024 (2017).","journal-title":"Metab. Clin. Exp."},{"key":"78419_CR23","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.mam.2019.07.002","volume":"68","author":"IHN Luijten","year":"2019","unstructured":"Luijten, I. H. N., Cannon, B. & Nedergaard, J. Glucocorticoids and brown adipose tissue: Do glucocorticoids really inhibit thermogenesis?. Mol. Aspects Med. 68, 42\u201359. https:\/\/doi.org\/10.1016\/j.mam.2019.07.002 (2019).","journal-title":"Mol. Aspects Med."},{"key":"78419_CR24","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.cmet.2015.07.002","volume":"22","author":"EP Broeders","year":"2015","unstructured":"Broeders, E. P. et al. The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Cell Metab. 22, 418\u2013426. https:\/\/doi.org\/10.1016\/j.cmet.2015.07.002 (2015).","journal-title":"Cell Metab."},{"key":"78419_CR25","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1093\/advances\/nmy067","volume":"10","author":"FJ Osuna-Prieto","year":"2019","unstructured":"Osuna-Prieto, F. J. et al. Activation of human brown adipose tissue by capsinoids, catechins, ephedrine, and other dietary components: A systematic review. Adv. Nutr. 10, 291\u2013302. https:\/\/doi.org\/10.1093\/advances\/nmy067 (2019).","journal-title":"Adv. Nutr."},{"key":"78419_CR26","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1007\/s00592-019-01418-2","volume":"56","author":"JC de-Lima-Junior","year":"2019","unstructured":"de-Lima-Junior, J. C. et al. Effect of pioglitazone treatment on brown adipose tissue volume and activity and hypothalamic gliosis in patients with type 2 diabetes mellitus: A proof-of-concept study. Acta Diabetol. 56, 1333\u20131339. https:\/\/doi.org\/10.1007\/s00592-019-01418-2 (2019).","journal-title":"Acta Diabetol."},{"key":"78419_CR27","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.molmet.2018.04.004","volume":"12","author":"M de Ligt","year":"2018","unstructured":"de Ligt, M. et al. Resveratrol improves ex vivo mitochondrial function but does not affect insulin sensitivity or brown adipose tissue in first degree relatives of patients with type 2 diabetes. Mol. Metab. 12, 39\u201347. https:\/\/doi.org\/10.1016\/j.molmet.2018.04.004 (2018).","journal-title":"Mol. Metab."},{"key":"78419_CR28","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/s12020-018-1698-x","volume":"62","author":"P Santhanam","year":"2018","unstructured":"Santhanam, P., Ahima, R. S., Mammen, J. S., Giovanella, L. & Treglia, G. Brown adipose tissue (BAT) detection by (18)F-FDG PET and thyroid hormone level(s)-a systematic review. Endocrine 62, 496\u2013500. https:\/\/doi.org\/10.1007\/s12020-018-1698-x (2018).","journal-title":"Endocrine"},{"key":"78419_CR29","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1016\/j.cell.2018.10.016","volume":"175","author":"Y Li","year":"2018","unstructured":"Li, Y. et al. Secretin-activated brown fat mediates prandial thermogenesis to induce satiation. Cell 175, 1561\u20131574. https:\/\/doi.org\/10.1016\/j.cell.2018.10.016 (2018).","journal-title":"Cell"},{"key":"78419_CR30","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1038\/s41598-018-37924-6","volume":"9","author":"C Brendle","year":"2019","unstructured":"Brendle, C. et al. Impact of diverse chemotherapeutic agents and external factors on activation of brown adipose tissue in a large patient collective. Sci. Rep. 9, 1901. https:\/\/doi.org\/10.1038\/s41598-018-37924-6 (2019).","journal-title":"Sci. Rep."},{"key":"78419_CR31","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s00256-018-3046-x","volume":"48","author":"SA Bos","year":"2019","unstructured":"Bos, S. A., Gill, C. M., Martinez-Salazar, E. L., Torriani, M. & Bredella, M. A. Preliminary investigation of brown adipose tissue assessed by PET\/CT and cancer activity. Skelet. Radiol. 48, 413\u2013419. https:\/\/doi.org\/10.1007\/s00256-018-3046-x (2019).","journal-title":"Skelet. Radiol."},{"key":"78419_CR32","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.acra.2017.09.007","volume":"25","author":"C Brendle","year":"2018","unstructured":"Brendle, C. et al. Correlation of brown adipose tissue with other body fat compartments and patient characteristics: A retrospective analysis in a large patient cohort using PET\/CT. Acad. Radiol. 25, 102\u2013110. https:\/\/doi.org\/10.1016\/j.acra.2017.09.007 (2018).","journal-title":"Acad. Radiol."},{"key":"78419_CR33","doi-asserted-by":"publisher","first-page":"909","DOI":"10.2214\/AJR.11.7488","volume":"198","author":"V Gilsanz","year":"2012","unstructured":"Gilsanz, V. et al. The depiction of brown adipose tissue is related to disease status in pediatric patients with lymphoma. Am. J. Roentgenol. 198, 909\u2013913. https:\/\/doi.org\/10.2214\/AJR.11.7488 (2012).","journal-title":"Am. J. Roentgenol."},{"key":"78419_CR34","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1007\/s00259-015-3280-6","volume":"43","author":"L Jorgov","year":"2016","unstructured":"Jorgov, L. et al. Paediatric and adolescent Hodgkin lymphoma: Information derived from diffuse organ uptake of 18 F-fluorodeoxyglucose on pre-treatment and on interim PET\/CT. Eur. J. Nucl. Med. Mol. Imaging. 43, 1220\u20131230. https:\/\/doi.org\/10.1007\/s00259-015-3280-6 (2016).","journal-title":"Eur. J. Nucl. Med. Mol. Imaging."},{"key":"78419_CR35","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1007\/s11684-017-0555-2","volume":"12","author":"M Dong","year":"2018","unstructured":"Dong, M., Lin, J., Lim, W., Jin, W. & Lee, H. J. Role of brown adipose tissue in metabolic syndrome, aging, and cancer cachexia. Front. Med. 12, 130\u2013138. https:\/\/doi.org\/10.1007\/s11684-017-0555-2 (2018).","journal-title":"Front. Med."},{"key":"78419_CR36","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/s00256-019-03322-w","volume":"49","author":"K Chu","year":"2020","unstructured":"Chu, K., Bos, S. A., Gill, C. M., Torriani, M. & Bredella, M. A. Brown adipose tissue and cancer progression. Skelet. Radiol. 49, 635\u2013639. https:\/\/doi.org\/10.1007\/s00256-019-03322-w (2020).","journal-title":"Skelet. Radiol."},{"key":"78419_CR37","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s12885-020-6591-3","volume":"20","author":"A Ginzac","year":"2020","unstructured":"Ginzac, A. et al. A decrease in brown adipose tissue activity is associated with weight gain during chemotherapy in early breast cancer patients. BMC Cancer 20, 96. https:\/\/doi.org\/10.1186\/s12885-020-6591-3 (2020).","journal-title":"BMC Cancer"},{"key":"78419_CR38","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1530\/JOE-14-0538","volume":"224","author":"JL Barclay","year":"2015","unstructured":"Barclay, J. L. et al. Effects of glucocorticoids on human brown adipocytes. J. Endocrinol. 224, 139\u2013147. https:\/\/doi.org\/10.1530\/JOE-14-0538 (2015).","journal-title":"J. Endocrinol."},{"key":"78419_CR39","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1210\/en.2016-1209","volume":"157","author":"O Al-Massadi","year":"2016","unstructured":"Al-Massadi, O. et al. Pharmacological and genetic manipulation of p53 in brown fat at adult but not embryonic stages regulates thermogenesis and body weight in male mice. Endocrinology 157, 2735\u20132749. https:\/\/doi.org\/10.1210\/en.2016-1209 (2016).","journal-title":"Endocrinology"},{"key":"78419_CR40","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","volume":"127","author":"SH Swerdlow","year":"2016","unstructured":"Swerdlow, S. H. et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127, 2375\u20132390. https:\/\/doi.org\/10.1182\/blood-2016-01-643569 (2016).","journal-title":"Blood"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78419-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78419-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78419-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:53:41Z","timestamp":1670374421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78419-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,11]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["78419"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-78419-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,11]]},"assertion":[{"value":"28 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21802"}}